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TOPLINE:

In patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) intolerant to ibrutinib or acalabrutinib, zanubrutinib demonstrated favorable tolerability with only 40% of ibrutinib-intolerance and 28% of acalabrutinib-intolerance adverse events recurring. Disease control was achieved in more than 90% of patients, with 64% achieving partial or complete response.

METHODOLOGY:

• A phase 2, single-arm trial enrolled 71 patients with CLL/SLL who were intolerant to ibrutinib (n = 44), acalabrutinib (n = 17), or both (n = 10), with a median follow-up of 34.5 months.
• Participants received zanubrutinib 160 mg twice daily or 320 mg once daily, with treatment duration ranging from 0.1 to 51.1 months.
• Analysis included assessment of adverse event recurrence, disease control rate, overall response rate, and progression-free survival as key endpoints.
• Researchers defined intolerance as grade ≥ 2 nonhematologic toxicities lasting for > 7 days, grade ≥ 3 nonhematologic toxicity of any duration, or grade 3 neutropenia with infection or fever.

TAKEAWAY:

• Of 67 efficacy-evaluable patients, 94% achieved disease control, with 64% showing partial or complete response and 30% maintaining stable disease.
• Among ibrutinib-intolerant patients, 54% experienced no recurrence of intolerance adverse events with zanubrutinib, while 64% of recurring events occurred at a lower grade.
• In acalabrutinib-intolerant patients, 70% had no recurrence of intolerance adverse events, and 44% of recurring events occurred at lower severity.
• The 2-year duration of response event-free rate was 79% (95% CI, 62%-89%), and the 2-year progression-free survival event-free rate was 76% (95% CI, 62%-85%).

IN PRACTICE:

“These data demonstrate that patients intolerant of ibrutinib/acalabrutinib may benefit from switching to zanubrutinib therapy….Zanubrutinib’s milder toxicity profile compared with ibrutinib may be attributable to its higher BTK [Bruton tyrosine kinase] selectivity and decreased binding to off-target kinases,” the authors of the study wrote.

SOURCE:

This study was led by Mazyar Shadman, MD, Division of Medical Oncology, Fred Hutchinson Cancer Center, University of Washington, Seattle. It was published online in Blood Advances.

LIMITATIONS:

According to the authors, the median follow-up of 16.5 months in the acalabrutinib-intolerant cohort was shorter than previous long-term studies of BTK inhibitors, which could affect the assessment of adverse event recurrence patterns. Additionally, the retrospective collection of ibrutinib- and acalabrutinib-intolerance data could result in incomplete information. The researchers also noted that some intolerance adverse events might not have recurred if patients were rechallenged with the same drug, though this seems unlikely given the initial discontinuation despite best efforts to manage toxicities.

DISCLOSURES:

Shadman disclosed having relationships with AbbVie, Genentech, AstraZeneca, Genmab, Janssen, BeOne Medicines Ltd, Bristol Myers Squibb, MorphoSys/Incyte, Kite Pharma, Eli Lilly, Mustang Bio, Fate Therapeutics, Nurix, and Merck. The study was supported by BeOne Medicines Ltd. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.